Because the virus that causes AIDS, the human immunodeficiency virus (HIV), is almost always lethal, the development of attenuated virus vaccines for AIDS presents serious medical, scientific, and ethical issues. For example, a major concern would be the possibility, albeit theoretical, that an attenuated HIV may revert to a pathogenic form and thus cause disease. One approach that has been explored in the monkey model system for AIDS has been to attenuate the virus by deleting some of the genes not obligatorily required for virus replication. We are pursuing this approach for HIV, and as a first step are trying to determine how these genes are functioning during the life cycle of the virus. It is clear that in the future the FDA will have to assess the safety, feasibility, and efficacy of several live vaccines against HIV, and it is likely that attenuated HIV will be among them. Thus, our work will directly assist in this assessment. In addition, the genes that are likely to be deleted in any attenuated HIV vaccine are also themselves likely to be targets for future therapeutics, and therefore our work on their function will be pertinent to this aspect as well.